The major route of infection in humans is via mucosal surfaces. These are protected by secretory IgA produced locally by IgA-secreting plasma cells. The precursors of intestinal IgA plasma cells can first be identified as IgA-bearing B cells in gut-associated lymphoid tissue (GALT) such as Peyer's patches (PP) and its draining mesenteric lymph nodes (MN). Our work concerns both the regulation of IgA responses in GALT and the migration pathways of mucosa-seeking B cells in mice. We have been testing the proposition that GALT is enriched relative to peripheral lymph nodes (PN) in T helper (TH) cells uniquely adapted to helping IgA responses. Our results indicate that although GALT produces slightly more help for IgA relative to other isotypes than PN after stimulation with concanavalin A in vitro in the presence of added peritoneal exudate cells, GALT does not produce more T-cell help for IgA responses than PN after in vivo priming. Particulate antigens such as sheep erythrocytes (SRBC) effectively prime both GALT and PN T cells to give help for all isotypes, and the ratios of plaque-forming cells (PFC) of different isotypes generated in a particular B-cell pool are the same. On the other hand, enteric exposure to soluble protein carriers results in such intense suppressive activity that little or no TH priming is induced in GALT. Subcutaneous priming of PN T cells yields good help for IgA responses and this help involves generation of IgA PFC from a surface IgA-negative B-cell population, implying that "switch" T cells may be present in PN T-cell populations. Our results indicate that PN T cells induced by soluble protein carriers and PN T cells induced by SRBC help different ratios of IgA PFC to PFC of other isotypes in the same population of B cells. We believe that different subsets of B cells with different capacities to generate IgA PFC may be responding to the different kinds of TH cells, and are exploring this possibility further. We are investigating various methods of preventing induction of suppression via the enteric route and are trying to clone a hybridoma with mucosa-seeking properties in order to establish a homogeneous cell line from which we can prepare moieties involved in the migration phenomena. Our work is of importance to the development of effective vaccines for use via the enteric route.